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Biomedical subjects

J Menczer

Publications and source records attributed to J Menczer.

At least 19 recordsLinked to original sources
PubMed2005

Management of endometrial carcinoma with cervical involvement. An unsettled issue.

The purpose of the present report is to review the various management options of endometrial carcinoma with cervical involvement. A Medline literature search for publications dealing with endometrial carcinoma (EC) with cervical involvement and treatment was made. Although many publications deal with EC with cervical involvement there is a lack of prospective controlled trials. Only one prospective randomized phase III trial has been published. The inaccuracies of clinical staging, the scarcity of reports with surgically staged patients, the multiple types of cervical involvement and prognostic indicators and the remarkable variations in treatment render it difficult to compare outcome results between publications. The small number of patients in many of these studies and their retrospective uncontrolled nature add to this difficulty. There are conflicting reports with regard to factors affecting outcome, also complicating the management issue of endometrial carcinoma with cervical involvement and comparison of treatment results. The optimal management of EC with cervical involvement remains to be established.

Antineoplastic Agents↗
PubMed2003

Premalignant lesions of the uterine cervix in a large cohort of Israeli Jewish women.

Israeli Jewish women are at low risk for cancer of the uterine cervix. In view of absent screening programs in Israel, there are only scarce data available with regard to results of PAP smears. The aim of this study was to assess the incidence of premalignant cervical lesions in the largest sample of PAP smears reported so far from Israel. We retrospectively analyzed the results of 297,849 PAP smears, which had been examined in a single laboratory, during 9 years (1991-1999). The incidence of low- and high-grade squamous intraepithelial was 0.69% and 0.29%, respectively. Our data indicate similar incidence rates for premalignant lesions in Jewish Israeli women as observed in Western countries, but no increase during the study period. In spite of relatively high incidence rates for premalignant lesions of the uterine cervix, the incidence rate for invasive cervical cancer remains conspicuously low. For unknown reason the conversion rate from premalignant cervical lesions to invasive cancer is lower in Israeli Jewish women than in European and North American women. We discuss possible reasons for this phenomenon and suggest that at this time mass screening for cervical cancer in Israel may probably not be justified.

Adult↗
PubMed2003

Frequency of BRCA mutations in primary peritoneal carcinoma in Israeli Jewish women.

OBJECTIVE: The aim of the present study was to compare demographic and clinical characteristics of primary peritoneal carcinoma (PPC) to ovarian carcinoma (OvC) with regard to BRCA mutation frequencies. METHODS: Incident cases of histologically confirmed cancer of the ovary or peritoneum diagnosed in Israeli Jewish women between March 1, 1994, and June 30, 1999, were identified within the framework of an ongoing nationwide epidemiological study of these neoplasms in Israel. The present study comprises 609 (81.5% of 747) Jewish women with epithelial stage III-IV OvC and 68 (77.3% of 88) Jewish women with PPC who were genetically tested for the BRCA mutations. Data from each patient were collected by the aid of a prestructured questionnaire and medical records. Blood samples or tumor tissue was tested for the 185delAG and 5382insC mutations in BRCA1 and the 6174delT mutations in BRCA2. RESULTS: A carrier rate of 28% of any BRCA 1/2 mutation was observed among the PPC group and of 30% among the invasive stage III-IV OvC. No differences were found between PPC and OvC neither in the overall distribution of BRCA1/2 mutation carrier rates nor according to type of mutation, age, ethnic origin, and histologic subtype. Among women with a positive family history, a higher rate of mutation carriers was observed in the PPC group compared to the OvC group (72.7 vs 43.8%, respectively, P = 0.07). CONCLUSIONS: The similar frequency distribution of BRCA1/2 mutations in PPC and OvC observed in the present study indicates that these mutations may predispose to PPC as well and that this neoplasm is part of the hereditary breast-ovarian cancer syndrome.

Adult↗
PubMed2003

Reflections on the FIGO surgical staging of invasive epithelial ovarian cancer.

The main aims and requirements of any staging system are: to determine the anatomical extent of disease, to allow uniform reporting of treatment results, comparison of their efficacy and pooling of data from various institutions. It should be based on the mode of spread of the neoplasm, take into consideration prognostic risk factors and be of prognostic value. A critical review of the FIGO staging system for ovarian carcinoma indicates that these aims and requirements are not entirely fulfilled. Following are some examples. It does not include exact recommendations for comprehensive surgical staging in apparently early ovarian cancer and staging is therefore not performed uniformly. The presence of parenchymal liver and lung metastasis may be facilitated by modern imaging devices. However, according to FIGO rules only simple X-ray procedures are allowed preoperatively. The correlation between increasing stage and survival is inconsistent and sometimes contrary to that expected. Many known prognostic factors are not included in the present staging system. Although the aims of data pooling and of uniform reporting of treatment results have been achieved, the validity of some comparisons are questionable in view of the variations in staging. The intent of this review was not to belittle the major contribution of staging to research, understanding and management of ovarian carcinoma, but to highlight its deficiencies. New data have accumulated since the FIGO staging system of ovarian carcinoma has been adopted and should prompt consideration of modifications such as incorporation of modern diagnostic procedures and of some established prognostic markers and reshuffling of certain substages.

Biopsy, Needle↗
PubMed2002

Effect of BRCA mutations on the length of survival in epithelial ovarian tumors.

PURPOSE: To study the role of BRCA mutations in ovarian cancer survival. PATIENTS AND METHODS: Blood samples and specimens of ovarian tumors (whenever blood samples were not available) at the time of the primary surgery were obtained in the course of a nationwide case-control study of women with ovarian cancer in Israel. The three common BRCA mutations in Israel (185delAG, 5382insC, and 6174delT) were analyzed with a multiplex polymerase chain reaction to amplify the exons containing the three mutations using fluor-labeled primers in a single reaction. Because each mutation is a small insertion or deletion, they can be detected as length polymorphisms. Patients were followed for up to 5 years (range, 20 to 64 months). Statistical analysis was performed using the Kaplan-Meier method and the log-rank test. Stepwise Cox regression analysis was used for determination of independent prognostic factors. RESULTS: This report is based on 896 blood or tumor specimens analyzed for the presence of the BRCA mutations. Of these, 234 women (26.1%) were found to be positive. A significant difference in survival pattern was found between BRCA1/BRCA2 carriers and noncarriers among the women with invasive ovarian cancer (median survival, 53.4 months v. 37.8 months; 3-year survival, 65.8% v. 51.9%, respectively). These differences were independent of age at diagnosis or stage of the disease. CONCLUSION: Our data indicate that the survival of patients with ovarian cancer is affected by BRCA germline mutation, at least in the early years after diagnosis.

Case-Control Studies↗
PubMed2002

Conversion of laparoscopy to laparotomy due to adnexal malignancy.

PURPOSE: The purpose of the present report was to assess the conversion rate from laparoscopy to laparotomy due to adnexal malignancy and to identify factors that might assist in the selection of the appropriate operative approach in patients with suspicious adnexal masses. METHODS: A retrospective review of the medical records of women who underwent laparoscopy due to ultrasonically complex adnexal masses. Ninety-five consecutive patients fulfilling these criteria, were identified. A comparison of patients with benign tumors who had laparoscopy only to those with invasive malignancies in whom laparoscopy was converted to laparotomy was performed. RESULTS: Malignancy was diagnosed in 18 (18.9%) patients. In 13 patients with malignancy (two borderline and 11 invasive), comprising 72.2% of the malignancies and 13.7% of the total group with complex adnexal masses, the laparoscopy was converted to laparotomy. Age of more than 50 years and a serum CA125 level above 35 U/ml were significantly more common in the malignant than in the benign group (90.9% vs. 15.6% and 63.6% vs. 11.6%, respectively; p < 0.0001 and p < 0.003, respectively). When both factors were present, the sensitivity and specificity for malignancy were 73.3% and 93.2%, respectively, and the positive and negative predictive values 73.3% and 95.6%, respectively. CONCLUSION: When an ultrasonically complex adnexal mass is encountered, predictive factors for malignancy should be taken into account before the mode of intervention is chosen. The conversion from laparoscopy to laparotomy because of an invasive malignant tumor is acceptable, if it is performed immediately and a gynecologic oncologist is on stand-by.

Adnexal Diseases↗
PubMed2002

p53 expression in tissue adjacent to endometrial carcinoma.

OBJECTIVE: Since several investigations did not demonstrate the presence of altered p53 in endometrial hyperplasias, it has been concluded that these alterations constitute a relatively late event in endometrial carcinoma. The aim of the present study was to assess the presence of p53 in the tissue adjacent to endometrial carcinoma in attempt to elucidate the relationship between these tissues. METHODS: New slides were prepared from paraffin-embeded tissue blocks of 49 endometrial endometrioid carcinoma hysterectomy specimens so that in each case tumor tissue and adjacent uninvolved endometrium were represented. Immunohistochemical staining for p53 detection was then performed. RESULTS: In 43 of the 49 hysterectomy specimens evaluated, the tissue adjacent to the endometrial carcinoma was non hyperplastic and in six it was hyperplastic. Positive immunohistochemical staining was found in 22 (44.9%) of endometrial carcinomas and in eight (16.3%) of the adjacent tissues. A statistically significant higher percentage of hyperplastic adjacent tissues than non-hyperplastic adjacent tissues were immunohistochemically p53 positive (50.0% vs 11.3%; p = 0.047). CONCLUSIONS: Our findings may indicate that p53 alterations are not necessarily a late event in endometrial endometrioid carcinogenesis. Since a large proportion of tissues adjacent to endometrial carcinoma do not show p53 alterations, other early cellular events may also play a role.

Adult↗
PubMed2001

Parity, oral contraceptives, and the risk of ovarian cancer among carriers and noncarriers of a BRCA1 or BRCA2 mutation.

BACKGROUND: Multiparity and the use of oral contraceptives reduce the risk of ovarian cancer, but their effects on this risk in women with a BRCA1 or BRCA2 mutation are unclear. METHODS: We conducted a population-based case-control study of ovarian cancer among Jewish women in Israel. Women were tested for the two founder mutations in BRCA1 and the one founder mutation in BRCA2 that are known to be common among Jews. We estimated the effects of parity and oral-contraceptive use on the risk of ovarian cancer in carriers and noncarriers in separate analyses that included all control women, who did not have ovarian cancer. RESULTS: Of 751 controls who underwent mutation analysis, 13 (1.7 percent) had a BRCA1 or BRCA2 mutation, whereas 244 of 840 women with ovarian cancer (29.0 percent) had a BRCA1 or BRCA2 mutation. Overall, each additional birth and each additional year of use of oral contraceptives were found to lower the risk of ovarian cancer, as expected. Additional births were protective in separate analyses of carriers and noncarriers, but oral-contraceptive use appeared to reduce the risk only in noncarriers; among carriers, the reduction in the odds of ovarian cancer was 12 percent per birth (95 percent confidence interval, 2.3 to 21 percent) and 0.2 percent per year of oral-contraceptive use (-4.9 to 5.0 percent). CONCLUSIONS: The risk of ovarian cancer among carriers of a BRCA1 or BRCA2 mutation decreases with each birth but not with increased duration of use of oral contraceptives. These data suggest that it is premature to use oral contraceptives for the chemoprevention of ovarian cancer in carriers of such mutations.

Adult↗
PubMed2001

Expression of heparanase, Mdm2, and erbB2 in ovarian cancer.

Ovarian cancer is the most lethal of gynecological malignancies. Yet early diagnosis and prognosis are far from being satisfactory. Degradation of heparan sulfate proteoglycans by heparanase appears to play an important role in the invasiveness of tumor cells through the basement membrane and into the extracellular matrix. Recent cloning of the heparanase gene and generation of monoclonal antibodies against the enzyme permit to examine tumor cell expression of the enzyme. The aim of the present study was to assess heparanase activity and localization in various subtypes of epithelial ovarian cancer in correlation with oncogene expression. Histologically confirmed malignant ovarian tissue from ten women and tissue from 2 benign ovarian tumors and 4 normal ovaries were assessed for heparanase presence, activity and localization, incidence of apoptosis and expression of the oncogenes erbB2 and Mdm2. Heparanase immunohistostaining and activity were present in mucinous carcinomas and were more intense than in endometrioid and in serous carcinomas. The lowest activity was observed in benign ovarian tumors and normal ovaries. In ovarian carcinomas the enzyme was intensely concentrated in the cytoplasm of the cancerous cells. In contrast, in normal ovaries and benign tumors the enzyme was predominantly localized in endothelial cells lining blood capillaries. The rate of apoptosis was considerably higher in mucinous and endometrioid carcinomas, and was lower in serous and primary peritoneal carcinomas. Extremely high concentration of heparanase was often demonstrated in apoptotic cells. Endometrioid and serous carcinomas showed high expression of Mdm2 and erbB2 while mucinous carcinomas showed low expression. In benign ovarian tumors and normal ovaries the expression of both oncoproteins was extremely low. In conclusion ovarian carcinomas demonstrate higher levels of heparanase than benign tumors and normal ovaries suggesting that the enzyme may play an important role in metastatic spread of the cancerous cells. Apoptosis may be a significant part of the mechanism of the enzyme release into the extracellular space. Although heparanase activity seems to play an essential role in tumor progression, expression of oncogenes, such as erbB2 and Mdm2 seems to play the dominant role in the development of ovarian cancer.

Adenocarcinoma, Mucinous↗
PubMed2000

The presence of HPV 16, 18 and p53 immunohistochemical staining in tumor tissue of Israeli Jewish women with cervical and vulvar neoplasia.

The incidence of cervical neoplasia in Israeli Jewish women is persistently lower, while that of vulvar carcinoma is comparable to that in other populations. The aim of the present investigation was to assess the prevalence of HPV and of immunohistochemically detected mutant p53 in Israeli Jewish women with cervical and vulvar neoplasia compared with other populations. Tissue sections from formalin-fixed paraffin-embedded blocks of ten patients with CIN III, 29 with invasive squamous cell carcinoma, three with adenocarcinoma and 14 with invasive vulvar carcinoma, were examined for the presence of HPV 16 and HPV 18 DNA by PCR amplification, and for mutant p53 protein by immunohistochemical staining. HPV negative cases were re-examined with a sensitive primer. HPV DNA was detected in eight patients with CIN III and in 23 patients with invasive squamous carcinoma. In the remaining cervical squamous neoplasia tissue analysis with the sensitive primer could not be done. HPV DNA was also detected in two patients with adenocarcinoma and in nine (64.2%) patients with vulvar carcinoma. Positive p53 immunohistochemical staining was found only in one CIN III patient, in six (20.7%) squamous carcinoma and in 11 (78.6%) vulvar carcinoma patients. Of the p53 immunohistochemical staining positive tissues, two with cervical carcinoma and six with vulvar carcinoma were also HPV-positive. The prevalence of HPV and of positive p53 immunohistochemical staining in our series of Israeli Jewish women with cervical and vulvar neoplasia is similar to that in other populations, suggesting that the etiological factors are probably also alike.

Adult↗
PubMed1999

Metastatic trophoblastic disease following partial hydatidiform mole: case report and literature review.

A patient with a triploid partial hydatidiform who had lung metastasis is presented. Complete response was achieved with methotrexate chemotherapy. A review of the literature revealed only 11 previously reported cases. In many of them clinical data are missing. All had lung metastasis and 1 had in addition a metastasis in the vagina. Only 1 of these patients died of disease. The others responded well to chemotherapy. Metastatic trophoblastic disease following partial mole is very rare but the exact prevalence is not known. Since risk factors for developing metastatic trophoblastic disease subsequent to partial mole are not known, all patients should be followed.

Abortion, Missed↗
PubMed1999

Exaggerated placental site erroneously diagnosed as non-metastatic trophoblastic disease. A case report.

BACKGROUND: Exaggerated placental site (EPS) is classified as a non-neoplastic trophoblastic lesion, and histologically it consists of endometrial and myometrial invasion of intermediate trophoblasts and syncytiotrophoblasts and it differs morphologically from placental site trophoblastic tumors and placental nodules. The purpose of this report is to increase physicians' awareness of this lesion. CASE: A 48-year-old woman with post-molar rising betahCG titers and a clinical diagnosis of non-metastatic trophoblastic disease underwent hysterectomy. Final histopathology showed exaggerated placental site--a lesion often unfamiliar to clinicians. CONCLUSION: It is suggested that operative hysteroscopy may be useful in the diagnosis and management of EPS.

Diagnosis, Differential↗
PubMed1999

Hypersensitivity reaction to carboplatin. Results of skin tests.

Four patients with hypersensitivity reaction to carboplatin of variable severity, after previous uneventful cisplatin and carboplatin treatment, are described. Skin testing performed in two of the patients suggests a cross-reaction with cisplatin but was negative with carboplatin in one of them. The mechanism of hypersensitivity reaction to carboplatin is poorly understood and the issue of retreatment with carboplatin is controversial. Physicians should be aware of the possible hypersensitivity reaction to carboplatin and appropriate precautions should be taken.

Adult↗
PubMed1999

Childhood and adolescent ovarian malignant tumors in Israel. A nationwide study.

OBJECTIVES: To determine the incidence of ovarian malignant tumors in childhood and adolescence, to ascertain the frequency distribution of the various tumor types and to assess time trends in Israel on a nationwide basis. METHODS: The study group included all Israeli Jewish patients < or = 19 years old with histologically confirmed ovarian malignancies, diagnosed in Israel from 1970 to 1994. Data were obtained from the Israel Cancer Registry. The effects of age at diagnosis and period of diagnosis were analyzed using the Poisson regression. RESULTS: Among the 82 patients identified, the most frequent tumors (72.0%) were of germ cell origin and among those about one third were dysgerminomas. Epithelial tumors were diagnosed in 26.6% of the patients and most of these were borderline malignancies. The incidence rate (IR) for the total group of ovarian malignancies in the 0-19 age group was 0.52 and for ages 5-19 it was 0.71 per 100,000. After adjustment for age, a significant linear trend for a decrease of germ cell tumors over time was found, stemming from a decrease of dysgerminomas. A significant trend for increase in the IRs with age was also found. In addition, a steep rise in the age specific IRs of epithelial borderline tumors was noted in the last 5 year period. CONCLUSIONS: The IRs of ovarian malignancies in childhood and adolescence in Israel, as in other countries, is very low as compared to adults and the most common tumors are of germ cell origin while malignant epithelial tumors are very rare. A time period effect in the germ cell tumors that resulted from an inexplicable significant decrease in the age specific IRs of dysgerminomas, was observed. A significant increase in borderline tumors was also noted and may be attributed to greater awareness of pathologists to this entity.

Adolescent↗
PubMed1999

Lack of the predominant BRCA1 and BRCA2 mutations in Jewish ovarian carcinoma patients who previously underwent ovulation induction.

The objective of the present investigation was to assess the presence of BRCA mutations in ovarian carcinoma patients who were previously treated with fertility drugs. The presence of the predominant Jewish BRCA1 and BRCA2 mutations in archival paraffin-embedded tumor tissue of four Jewish women with ovarian carcinoma who previously underwent ovulation induction with clomiphene citrate, was determined. None of the tissues contained the mutations examined. This preliminary finding does not support the assumption that the presence of BRCA1 and BRCA2 mutations in some infertility patients treated by fertility drugs could explain the subsequent development of epithelial ovarian cancer in these women.

Adult↗
PubMed1998

Cancer incidence in a cohort of infertile women.

Among 2,496 infertile Israeli women treated between 1964 and 1974, 143 cancer cases were observed as compared with 116.1 expected (standardized incidence ratio (SIR) = 1.2, 95% confidence interval (CI) 1.0-1.5) through 1991. Site-specific analysis revealed 12 ovarian cancers versus 7.2 expected (SIR = 1.6, 95% CI 0.8-2.9), 21 endometrial cancers versus 4.3 expected (SIR = 4.85, 95% CI 3.0-7.4), and 59 breast cancers versus 46.6 expected (SIR = 1.3, 95% CI 0.96-1.6). Sensitivity analysis revealed that confounding was unlikely to explain the raised risk of endometrial cancer, but nulliparity might explain the increased risk of ovarian cancer. The excess of endometrial cancer was prominent among patients with normal estrogen production but progesterone deficiency (SIR = 9.4, 95% CI 5.0-16.0). The risk for ovarian cancer was similar among the total groups of treated and untreated patients (SIR = 1.7 vs. 1.6). The standardized incidence ratio for endometrial cancer was higher among the treated group than the untreated group, although not significantly. Treatment with ovulation-inducing drugs does not appear to increase the risk for ovarian cancer, but its role cannot be completely excluded.

Adult↗